Genetic factors contributed by both host and virus interact to determine the effects of murine leukemia virus (MuLV) infection of mice. Host genes which influence MuLV-related hematopoietic system disease have been identified and chromosomally mapped; these include MuLV ecotropic virus induction loci, which represent integrated proviral sequences, and genes controlling infection and spread of virus, such as Fv-1, determining sensitivity to infection by N- or B-tropic MuLVs, and Rmcf, which affects replication and generation of MCF viruses. In order to study gene effects isolated from other host genetic differences, a number of strains of NFS mice congenic for different virus induction genes and for Rmcfr from DBA/2 and CBA/N have been established or are being developed. In addition, ecotropic virus-free congenic lines of AKR/N, C57BL/10 and BALB/cPi are being developed. V-congenic mice have been widely used in studies of spontaneous neoplastic disease, in oncogenicity studies of various acute transforming and replication competent MuLVs, and in studies of the relation of endogenous MuLV to carcinogen-induced tumors. Other host factors controlling MuLV-related disease are less well characterized and studies of these factors are still concerned with defining strain distribution and genetic patterns. In progress is a study of the genetics of disease induced by MuLV containing the oncogene v-raf or a construct with both v-raf and avian v-myc sequences. Also under study is the strain distribution of sensitivity to an unusual lymphoproliferative and immunosuppressive disease, in which known host gene controls appear not to function wholly as expected.